At both mice and men age, many deleterious changes occur in their cells and tissues. This project will determine whether disparate types of changes occur at similar rates in the same animal, and will evaluate methods of inhibiting such changes. Physiological tests will be developed to measure accurately different types of age-related changes in genetically defined animals raised under strictly controlled conditions. Changes with age in collagen denaturation, kidney function, immune response, oxygen utilization, metabolically active mass and other parameters will be tested. The most useful tests are those that do not cause permanent damage to the subject. They make it possible to give different types of tests to the same individual, whose lifespan is then determined. If results of different tests were correlated with each other and with subsequent life expectancies, a series of such tests might measure physiological age and be useful to evaluate treatments designed to alter the aging rate. If no correlations were found, the tests would still be valuable in assaying the status of each system tested, and in evaluating treatments designed to alleviate problems in those systems. The effects of the following treatments will be studied: food restriction, immunological rejuvenation, hypophysectomy, parabiosis, and voluntary exercise. Genetic defects that may affect the aging rates of certain systems will also be tested. Whether changes with age are intrinsic in a tissue can be studied by comparing functional capacities of old and young tissues transplanted to young recipients. Hemopoietic stem cell lines appear to be unaffected by aging, but are significantly affected by transplantation; this effect will be studied. Using skin tissue, the effects of aging and transplantation on collagen solubility, DNA damage and fibroblast outgrowth will be assayed in collaborative studies.